CurrentBlue Cross Blue Shield - TexasPolicy CPCPLAB061

Testing for Alpha-1 Antitrypsin Deficiency

Criteria and reimbursement guidance for laboratory testing (serum AAT quantification, phenotyping/proteotyping) for suspected alpha-1 antitrypsin deficiency; applies to providers submitting claims to Blue Cross Blue Shield - Texas.

Policy Summary

PayerBlue Cross Blue Shield - Texas

PolicyTesting for Alpha-1 Antitrypsin Deficiency

Policy CodePolicy CPCPLAB061

Change TypeCoverage criteria updated (material changes)

Effective DateFeb 5, 2025

Next Review Date

Key ActionVerify product-specific prior authorization and submit clinical documentation supporting the indication when ordering AAT testing.

SourceLink

POLICY UPDATE CHANGES

Added 'once per lifetime' to the reimbursement allowance for initial AAT testing.

Expanded examples for 'unexplained liver disease' in the covered indications list.

Added neonatal cholestasis as a reimbursable indication.

1lifetime frequency

8listed indications

2testing pathways

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Coverage Criteria

Initial testing (covered with criteria)

Reimbursable once per lifetime when ANY one of the following is met:

Initial covered indications: a) Symptomatic individuals 18 years of age or older with emphysema, COPD, or asthma; b) Individuals with unexplained liver disease (e.g., chronic hepatitis with or without cirrhosis, chronically elevated aminotransferase levels, portal hypertension, primary liver cancer); c) Individuals with persistent obstruction on pulmonary function tests without identifiable risk factors (e.g., cigarette smoking, occupational exposure); d) Individuals 18 years of age or older with necrotizing panniculitis; e) Siblings of an individual with known alpha-1 antitrypsin (AAT) deficiency; f) Individuals with anti-proteinase three-positive vasculitis (C-ANCA-positive); g) Individuals with bronchiectasis without evident etiology; h) Individuals with neonatal cholestasis.once per lifetime

See Note 1 for preferred testing methods; applies to serum AAT quantification and AAT phenotyping or proteotyping.

Phenotyping/proteotyping after inconclusive/discordant genotype

Covered when ALL of the following are met:

Follow-up phenotyping/proteotyping: For individuals who have negative genotype results for common variants or who have discordant results between AAT serum levels and proteotype, but for whom clinical suspicion of AAT deficiency remains, isoelectric focusing (phenotyping) or proteotyping may be reimbursable.N/A

Phenotyping should be performed using isoelectric focusing; proteotyping for Z and S alleles should use LC-MS/MS (Note 1).

Not medically necessary / Not reimbursable

Not reimbursable:

Not reimbursable: Testing for alpha-1 antitrypsin (AAT) deficiency for all other situations not described in the covered indications or the follow-up allowance in #2 is not reimbursable.N/A

Claims submitted for indications outside the listed situations may be denied.

All situations not specifically listed under the reimbursable indications in this policy or the follow-up allowance for phenotyping/proteotyping after negative or discordant genotype results are excluded from reimbursement.

Testing performed for indications other than the enumerated list of reimbursable situations (the eight clinical indications in item 1) and the specified follow-up scenario in item 2 (negative genotype for common variants or discordant serum AAT level versus proteotype with ongoing clinical suspicion) is considered not reimbursable and claims may be denied.

Covered Indications (Initial AAT Testing)

Symptomatic adults (>=18) with emphysema, COPD, or asthma

Covered indication: Symptomatic individuals 18 years of age or older with emphysema, COPD, or asthma.>= 18 years

Meets initial testing allowance when criterion is satisfied (once per lifetime).

Unexplained liver disease

Covered indication: Individuals with unexplained liver disease (examples include chronic hepatitis with or without cirrhosis, chronically elevated aminotransferase levels, portal hypertension, primary liver cancer).N/A

Meets initial testing allowance when criterion is satisfied (once per lifetime).

Frequency Limits

inv-23: Serum AAT quantification and AAT phenotyping or AAT proteotyping for initial evaluation — Once per lifetime.

Covered testsSerum quantification of alpha-1 antitrypsin (AAT) protein and AAT phenotyping or AAT proteotyping for initial evaluation

Frequency limitOnce per lifetime for initial evaluation

ApplicabilityApplies when any one of the listed clinical indications (see coverage criteria) is met

Coding

inv-07: Age threshold for several indications — >= 18 years for symptomatic individuals with emphysema/COPD/asthma, necrotizing panniculitis, and siblings testing context.

Age threshold>= 18 years for symptomatic individuals with emphysema, COPD, or asthma

Necrotizing panniculitis>= 18 years for individuals with necrotizing panniculitis

Siblings testing context>= 18 years applies to siblings of an individual with known AAT deficiency when listed as a covered indication

Provider Actions

Prior Authorization

Prior Authorization / Product-Specific Requirements

Check product-specific prior authorization — review the member's plan documents and product terms prior to ordering testing. Lab management reimbursement criteria and prior authorization requirements may vary by product; when in doubt, verify eligibility and any prior authorization or precertification requirements with the member's plan.

Prior authorization requirements vary by product — consult the member's plan documents
Verify eligibility and any precertification/prior authorization prior to specimen collection or claim submission

Note

Documentation Required

Clinical Documentation Required

Clinical documentation required — providers must submit accurate clinical documentation supporting the medical indication for testing. Claims are subject to review and may be denied if documentation does not support medical necessity or if coding is incomplete or inconsistent with industry standards.

Ordering Requirements

Note

Confirm ordering and documentation requirements with the member’s plan

Providers should verify product-specific plan documents for any ordering or prior authorization requirements before ordering AAT testing and include clinical documentation with the order as required by the plan.

Confirm member eligibility and any plan-specific prior authorization requirements.
Include clinical indication and supporting documentation with the order to facilitate claim processing and potential reviews.

Background

Alpha-1 antitrypsin (AAT) deficiency is an inherited genetic disorder associated with lung disease (including emphysema, chronic obstructive pulmonary disease, and asthma) and liver disease (including chronic hepatitis, cirrhosis, and primary liver cancer). Clinical evaluation typically begins with serum AAT quantification, with follow-up molecular or protein-based methods — genotyping, phenotyping (isoelectric focusing), or proteotyping (LC‑MS/MS for common Z and S alleles) — as indicated by results and clinical suspicion.

Definitions

inv-13: AAT phenotyping (isoelectric focusing) — definition/key-value.

MethodAAT phenotyping should be performed using isoelectric focusing

PurposeUsed to identify AAT protein phenotypes when genotype is negative or results are discordant with serum levels

TerminologyAlso referred to as Pi-typing in some contexts

inv-14: AAT proteotyping (LC-MS/MS for Z and S alleles) — definition/key-value.

MethodAAT proteotyping (Pi-typing) for Z and S alleles should be performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS)

ScopeTargets common AAT alleles (Z and S) when proteotype information is needed

Not Covered

Testing for alpha-1 antitrypsin deficiency that does not meet one of the eight reimbursable indications listed in item 1 (e.g., symptomatic adults ≥18 with emphysema/COPD/asthma; unexplained liver disease; persistent unexplained obstruction on PFTs; adults ≥18 with necrotizing panniculitis; siblings of a person with known AAT deficiency; C‑ANCA–positive vasculitis; bronchiectasis without evident etiology; neonatal cholestasis) or the follow-up allowance in item 2 (phenotyping after negative or discordant genotype results when clinical suspicion persists) is not covered and will not be reimbursed.